Wolford R W, MacDonald M R, Zehfus B, Rogers T J, Ferro A J
Cancer Res. 1981 Aug;41(8):3035-9.
The effect of 5'-deoxy-5'-methylthioadenosine (MTA) on the growth of culture murine lymphoid cells was examined. MTA inhibited the growth of murine lymphoid cell lines of both B- and T-cell origin in a reversible, nontoxic, and dose-dependent fashion. When measured 2 days after the addition of MTA to the cells, the concentration that inhibited proliferation by 50% for MTA was about 250 muM. Cells incubated in the presence of 0.5 mM MTA for 1, 2, or 3 days were able to recover from the inhibitory effect of the nucleoside and resumed growth. Six structural analogs of MTA were also found to inhibit cell growth. Five of these analogs served as alternative substrates for MTA phosphorylase, while one, the 7-deaza analog (5'-deoxy-5'-methylthiotubercidin), was not a substrate for the phosphorylase but was a potent inhibitor of enzyme activity. Inhibition of growth by 5'-deoxy-5'-methylthiotubercidin was dose dependent (the concentration that inhibited proliferation by 50% approximately or equal to 10 muM) and at 50 muM was reversible and nontoxic.
研究了5'-脱氧-5'-甲硫基腺苷（MTA）对培养的小鼠淋巴细胞生长的影响。MTA以可逆、无毒且剂量依赖性的方式抑制B细胞和T细胞来源的小鼠淋巴细胞系的生长。在向细胞中添加MTA后2天进行测量时，MTA抑制增殖50%的浓度约为250μM。在0.5 mM MTA存在下孵育1、2或3天的细胞能够从核苷的抑制作用中恢复并恢复生长。还发现MTA的六种结构类似物抑制细胞生长。这些类似物中的五种作为MTA磷酸化酶的替代底物，而其中一种，即7-脱氮类似物（5'-脱氧-5'-甲硫基杀结核菌素），不是磷酸化酶的底物，但却是酶活性的有效抑制剂。5'-脱氧-5'-甲硫基杀结核菌素对生长的抑制作用是剂量依赖性的（抑制增殖50%的浓度约等于10μM），并且在50μM时是可逆且无毒的。
